The present invention encompasses articles designed to provide controlled release of surfactant compounds. More specifically, the articles herein comprise a microporous membrane releasably enclosing a solution of a micelle-forming surfactant compound.
The desirability of providing metered dosage forms of biologically active or medicinal agents has long been recognized. Metered dosages can be manifest either as controlled release or sustained release of a given material. The distinction between "controlled release" and "sustained or prolonged release" has been recognized; see Cowsar, in "Advances in Experimental Medicine and Biology", Vol. 49, "Controlled Release of Biologically Active Agents", Ed. Tanquary and Lacey, Plenum Press, New York 1974. However, the terms are frequently used interchangeably. For the present purposes, "sustained release" articles are defined as those which prolong the time period over which a material is released into an external environment. Sustained release can be accomplished by incorporating a kinetic barrier to release within the article, e.g., diffusion through a polymer matrix. Conversely, the term "controlled release" as used herein encompasses articles which release material to an external environment in response to "need". In the controlled release system there is no persistent kinetic barrier to release within the article; instead, initial release to achieve an effective concentration of the material is rapid, and an external parameter controls this release. For example, in the medical uses of the present articles the concentration of active compound in the body fluids bathing the product is the controlling parameter. The major distinction between the two types of systems is that articles based on the controlled release principle operate by a feedback mechanism regulating release, whereas articles employing the sustained release mechanism do not. One parameter of the total system is influential with respect to whether controlled or sustained release ensues, namely, the volume of the external fluid. When the ratio of this volume to the membrane area available for diffusion is too high, feedback control never develops, and sustained, rather than controlled release, ensues.
Controlled release articles of the present type respond rapidly to changes such as dilution effects in the environment external to the article, e.g., by body fluid changes, whereas sustained release articles do not. The net result is that articles based on the principle of controlled release are capable of rapidly establishing an effective level or concentration of a medicament or other agent in a selected environment, and then shutting off release so as to maintain the concentration at that level. In contrast, sustained release articles simply dispense an agent at a constant rate. Such articles, therefore, do not display the feedback regulation of release that a controlled release article displays.
It will be recognized that articles operating by the controlled release mechanism provide substantial advantages over sustained release articles for certain uses. For example, placement of a properly formulated controlled release medicament system in an animal's body cavity in contact with body fluids very quickly establishes an effective concentration of the medicament in the fluids. This concentration is automatically maintained in response to dilution or depletion as additional fluids are secreted, or the medicament is bound to tissue, absorbed, etc. Accordingly, for uses such as in contraceptives where it is desirable to provide an effective amount of the contraceptive agent almost immediately, a controlled release system rather than a sustained release system is preferred.
It has now been discovered that solutions of micelle-forming surfactant compounds can be releasably enclosed in a container comprising a microporous membrane. Articles prepared in this manner are stable and do not suffer osmotic rupture when placed in body cavities in contact with body fluids. Rather, the stable articles provide controlled release of the surfactant into the body fluids. Proper selection of surfactant provides a means for achieving various biological effects, e.g., antimicrobial activity, spermicidal activity, and the like. While it will be recognized that the articles herein can be used in any situation where controlled release of a surfactant into an external fluid medium is desired (as long as the previously noted volume to area ratio is appropriate), the preferred articles are especially adapted for use in body cavities such as the vagina.
It is an object of the present invention to provide stable articles which furnish controlled release of a micelle-forming surfactant.
It is another object herein to provide articles adapted for use in contact with living tissue (human or lower animal) which furnish controlled release of biologically active surfactants.
It is another object herein to provide articles suitable for use as contraceptives.
These and other objects are obtained herein as will be seen from the following disclosures.